Cortisol, also known as hydrocortisone, is a glucocorticoid of the adrenal cortex that is a derivative of cortisone. At normal physiological levels (2-25 mg/dl) cortisol is a naturally occurring anti-inflammatory steroid. However, when cortisol is present in the blood at elevated levels, above about 30 mg/dl, it acts as a catabolic stress hormone, cannibalizes muscle tissue and can destroy practically every cell, tissue and organ in the human body. For example, high cortisol levels can result in the breakdown of connective tissue, lowered immunity, reduced muscle RNA synthesis, redistribution of fat and other maladies. In the human immune system elevated levels of cortisol can induce a lowering of the number of CD4 cells, elevation of CD8 cell levels, and disappearance of natural killer cells. These are symptoms often found in HIV and AIDS patients.
Elevated cortisol levels are found in many diseases, including aging related conditions and depression. White it was initially thought that elevated cortisol was the result of these diseases, there is now evidence that high cortisol levels actually play a role in causing these diseases. As such, it had been suggested that tracking and treating increased levels of cortisol could be used to treat or prevent high cortisol diseases such as cancer, ulcers, myocardial infarction, diabetes, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), strokes, psoriasis, Alzheimer's disease, Space Adaption Syndrome, and the like, where elevated cortisol is constantly found.
Blood serum cortisol levels are considered “normal” in the 2-25 mg/dl range, with 7-25 mg/dl being normal for the morning hours (8:00 a.m.), and 2-9 mg/dl being normal for the afternoon hours (5:00 pm).
In order to reduce the effects of prolonged high cortisol levels, a cortisol antagonist or cortisol blocker or anti-cortisol compound would be beneficial to the patient. Even more beneficial to the patient would be a mixture of cortisol antagonists that act synergistically. As used herein and in the claims, the term “cortisol blocker” means any known chemical entity or combination of entities that, when administered to an individual, will retard or prevent the production of cortisol or inhibit or prevent the catabolic activity of cortisol. Specific examples of cortisol blockers include RU 486, DHEA, ketaconazole, procaine hydrochloride, zinc and salts of zinc, acorbic acid, Ipriflavone, HMB, phosphatidylserine and others as more fully described below. An aspect of the present invention is directed to the use of at least one, preferably a combination of cortisol antagonists in combination with anti-HIV drugs, to minimize the side effects of the anti-HIV drug therapy.
Drug treatment for human immunodeficiency virus (HIV), the etiologic agent of the acquired immunodeficiency syndrome (AIDS) and AIDS related complex includes azidothymidine (3′-azido-3′-deoxythymidine; zidovudine (Retrovir)) or AZT. While clinical benefits against AIDS have been reported, serious adverse reactions, particularly bone marrow suppression, have been observed. In a study of the toxicity of AZT in the treatment of AIDS patients, nausea, myalgia, insomnia, Cushings like symptoms and severe headaches have been reported by recipients of AZT when compared to those on placebo. Anemia typically develops in 24% of AZT recipients often requiring multiple red blood cell transfusions.
It has also been reported that people taking combination or “cocktail” drug treatments for HIV infection, develop bizarre symptoms that evidence dangerous disruption of the patient's lipid metabolism. Symptoms such as loss of subdermal fat for most of the body, development of hardened fat deposits in the stomachs and on the necks, elevations in triglycerides and cholesterol, and insulin intolerance have been reported. The “buffalo humps” and “protease paunches” appear to be disruptions of fat metabolism caused by the use of drugs for the treatment of HIV infections.
The fat metabolism side effects have been directly linked to four (4) anti-HIV drugs called protease inhibitors. Those protease inhibitors include Indinavir, Viracept, Ritonavir and Saquinavir. A consequence of an imbalance in fat metabolism is akin to Cushing's like disease or Cushingoid manifestations. Other side effects associated with these anti-HIV drugs include changes akin to a pre-diabetes state. Triglycerides and higher cholesterol levels have also been reported. While not actually Cushings disease, which is a high cholesterol disorder that causes similar “buffalo humps”, the actual mechanism for the observed side effects of the anti-HIV drugs is not understood.
It is not unusual for HIV infected individuals to receive a number of cocktail of the anti-HIV drugs, also known as anti-HIV cocktails. Some investigators have speculated that the association between the administration of the anti-HIV cocktails and the development of the Cushingoid-like symptoms suggests that the anti-HIV drugs are likely responsible for the fat redistribution in the patients.